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Microsurgical management of 883 previously coiled intracranial aneurysms: a systematic review, meta-analysis, and meta-regression of its effectiveness and safety
No full textOBJECTIVE: With the increasing number of intracranial aneurysms (IAs) treated by endovascular coiling, more residual and recurrent IAs are being encountered. This study aimed to evaluate the effectiveness and safety of the microsurgical management of these previously coiled IAs. METHODS: Systematic searches of the Medline, Embase, and Cochrane Central databases were performed. The primary outcome was good functional outcome (modified Rankin Scale score 0-2 or Glasgow Outcome Scale score 4-5) and unchanged/improved functional outcomes at the last follow-up. Secondary outcomes included intraoperative rupture, complete occlusion confirmed on imaging, and perioperative complications and death within 30 days. RESULTS: Thirty-nine studies reporting on 874 patients with 883 previously coiled IAs managed by microsurgery were included in the meta-analysis. Of the 883 IAs, 656 (74.3%), 167 (18.9%), 44 (5.0%), and 16 (1.8%) underwent direct clipping, clipping with coil removal, bypass, and trapping, respectively. Forty-five (5.1%), 806 (91.3%), and 32 (3.6%) IAs were classified as Gurian group A, B, and C. IAs were located anteriorly in 88.2% and posteriorly in 11.8%; 45.3% were \u3c 7 mm, 31.3% were 7-12 mm, 14.6% were 13-24 mm, and 8.8% were \u3e 25 mm. The overall mean clinical follow-up duration was 33.7 months. Overall proportions of intraoperative rupture, perioperative stroke, and death were 0.1% (95% CI 0.0%-1.1%, I2 = 25.2%), 8.2% (95% CI 5.85%-11.34%, I2 = 52.8%), and 3.7% (95% CI 2.63%-5.24%, I2 = 0.0%), respectively. The proportions of complete occlusion, good, and improved/unchanged functional outcomes were 97.2% (95% CI 95.82%-98.13%, I2 = 0.0%), 82.9% (95% CI 79.67%-85.69%, I2 = 5.1%), and 92.3% (95% CI 89.27%-94.54%, I2 = 0.0%), respectively. Direct clipping of unruptured anterior circulation IAs was associated with the lowest proportion of intraoperative rupture, perioperative stroke, and death. Direct clipping was also associated with the greatest proportion of complete occlusion, good functional outcome, and improved/unchanged neurological outcome. Microsurgery within 1 month of endovascular coiling and management of Gurian group C IAs were associated with greater proportions of perioperative death. CONCLUSIONS: Microsurgical management of previously coiled IAs is an effective and safe strategy in well-selected patients. Important factors to consider in the management of these IAs include the size and location of the IA, rupture status at initial presentation, indication for microsurgery, and type and timing of microsurgery
Prone lateral transpsoas interbody fusion with robotic assistance
No full textThis video demonstrates robotic assistance for performing single-position prone lateral transpsoas interbody fusion with posterior percutaneous screws. The ability to preoperatively plan the screws and interbody devices may help surgeons improve accuracy as well as increase the ease of performing these single-position minimally invasive procedures. The video can be found here: https://stream.cadmore.media/r10.3171/2025.4.FOCVID2515
Anatomical Location of the Bowel in Different Surgical Positions: Implications for Lateral Access in Prone Single-Position Surgery
No full textSTUDY DESIGN: Radiographic analysis. OBJECTIVE: Evaluate the anatomical relationships of the bowel to the lateral surgical corridor and the spine in various surgical positions. SUMMARY OF BACKGROUND DATA: Retroperitoneal transpsoas lateral lumbar interbody fusion (LLIF) may be performed with patients in the prone position, allowing for lateral and posterior approaches to the spine without repositioning the patient. Few, if any, studies discuss changes of the bowel position during these procedures. METHODS: Ten healthy volunteers underwent MRI in 3 positions: supine, prone with hips extended (prone-extension), and right lateral decubitus (left side up) with hips flexed (lateral decubitus-flexion). Anatomical relationships of the bowel to fixed spinal landmarks were assessed at L1-5, and the changes among participants\u27 positions were compared. RESULTS: Anterior bowel movement was noted with prone-extension (range: 0.32-1.39 cm) and lateral decubitus-flexion (range: 0.97-2.18 cm) positioning compared with supine positioning. Significant anterior movement of the bowel was observed at L1-2 (P=0.03) and L2-3 (P=0.04) disc levels in participants in the prone position and at L2-3 (P=0.002) and L3-4 (P=0.01) in those in the lateral position when compared with those in the supine position. No differences in bowel movement were found for prone and lateral positioning. The percentages of participants with bowels located in the operative corridor were similar among the surgical positions (all P\u3e0.07). 3D volumetric analysis showed that the magnitude of these changes was greatest for the upper left colon. CONCLUSIONS: The results showed that the bowel was positioned anteriorly at L1-5 disc levels when participants were in prone-extension and lateral decubitus-flexion positions compared with the supine position. Overall, the magnitude of bowel positional change was small and variable. These findings suggest that the bowel does not fall away from the surgical corridor when performing retroperitoneal access for single-position prone surgery compared with the lateral decubitus-flexion position
Perioperative Transfusion Following Total Laryngectomy: A Nationwide Study.
No full textOBJECTIVE: Total laryngectomy (TL) represents a major operation often performed on medically complex patients. The impact of blood transfusion in TL patients is not well defined. Here, we utilize a national database to characterize these patients and further investigate a potential dose-dependent relationship between transfusion and postoperative outcomes.
METHODS: The National Surgical Quality Program (NSQIP) was queried for patients who underwent TL with/without neck dissection (CPT 31360, 31365) between 2014 and 2022. Total units of transfused blood were only available for patients between 2020 and 2023. Statistical analysis involved hypothesis testing, multivariate logistic regression, and receiver operating characteristic (ROC) analysis.
RESULTS: Among 2311 patients, 413 (17.9%) received transfusions. Non-White race, ASA Class ≥ 3, hypertension, cancer with distant metastases, bleeding disorders, and elevated BUN, WBC, and INR were associated with transfusion (p \u3c 0.05). Multivariate analysis identified hypertension (OR 1.81), bleeding disorders (OR 2.64), ASA ≥ 3 (OR 2.40), concurrent free flap (OR 3.75) and lower hematocrit (OR 0.85) as predictors. Transfused patients had longer hospital stays (12 vs. 9 days), increased complications (e.g., stroke, DVT), higher reoperation (23.2% vs. 13.9%) and mortality (2.7% vs. 0.8%) (p \u3c 0.05). ROC analysis suggested transfusion \u3e 2.5 units was associated with adverse outcomes.
CONCLUSION: TL remains a major surgical endeavor that can be associated with lengthy and complicated hospital courses. We show that perioperative transfusion may be associated with increased hospital stay, reoperation, and mortality in TL patients, with a potential dose-dependent effect. Our study reinforces the risks associated with blood transfusion and further supports the thoughtful utilization of blood products in TL patients
Cognitive impairment and p-tau217 are high in a vascular patient cohort
No full textINTRODUCTION: Vascular comorbidities are modifiable contributors to cognitive impairment and Alzheimer\u27s disease (AD), yet brain health outcomes are rarely evaluated in cardiovascular patients. METHODS: This study prospectively evaluated cognition and AD pathology in 162 community-dwelling adults with asymptomatic cardiovascular disease who did not have a clinical diagnosis of dementia or cognitive impairment. RESULTS: Twenty-nine percent of the cohort had Montreal Cognitive Assessment (MoCA) scores indicative of cognitive impairment or dementia after adjusting for age, sex, and education based on National Alzheimer\u27s Coordinating Center normative data. AD blood biomarker phosphorylated tau217 was elevated in 55% of the cohort, significantly associated with decreased MoCA scores (β = -1.46, 95% confidence interval [CI] -2.53 to -0.39, p \u3c 0.01), and accurately differentiated cognitive impairment (area under the curve 0.94, 95% CI 0.88-0.99). DISCUSSION: This level of undiagnosed cognitive impairment and AD pathology exceeds what would be expected in the general population and highlights a potential need for screening and future work to better identify treatment options. HIGHLIGHTS: Brain health outcomes are rarely evaluated in vascular patients. One hundred sixty-two adults with asymptomatic cardiovascular disease but without diagnoses of cognitive impairment or dementia were evaluated. Phosphorylated tau217 accurately differentiated cognitive impairment in patients with cardiovascular disease. High levels of cognitive impairment and Alzheimer\u27s disease pathology are greatly underdiagnosed in the cardiovascular population
Active Immunization Targeting Amyloid β for the Treatment of Alzheimer\u27s Disease
No full textBACKGROUND: Alzheimer\u27s disease (AD) is the most prevalent neurodegenerative condition worldwide. It is characterized by the formation of amyloid beta (Aβ) plaques in the brain and by the accumulation of neurofibrillary tangles; the disease is marked by cognitive decline and memory impairment over time. Although cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists have been used to relieve symptoms, immunotherapies to treat the disease itself by targeting removal of amyloid are now beginning to be applied clinically. However, methods that allow the control of AD symptoms and that would require only a few clinical follow-ups are often preferred by patients. Thus, active immunization, or vaccination, against Aβ and tau is still being explored as a possible therapeutic intervention. SUMMARY: This review aims to describe ongoing and discontinued immunization trials to treat AD. We conducted a comprehensive review of the literature to analyze the current status of vaccinations for AD. We examined and summarized the studies and clinical trials that explored the efficacy, safety, and challenges associated with this therapeutic approach. KEY MESSAGES: This review highlights the potential for vaccination development to treat AD, including its efficacy, associated complications, and limitations. Much progress has been made over the past 2 decades, but challenges remain. Immunization is a promising avenue for treating or preventing symptomatic AD, offering potential benefits beyond symptomatic relief. Because challenges such as immunogenicity and safety profiles need to be addressed, further research and development are necessary to meet the growing demand for patient-acceptable, effective AD treatments
Efficacy and Safety of Zilucoplan in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial
No full textIMPORTANCE: The etiology of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, is unknown. However, neuroinflammation and complement activation may play a role in disease progression. OBJECTIVE: To determine the effects of zilucoplan, an inhibitor of complement C5, in individuals with ALS. DESIGN, SETTING, AND PARTICIPANTS: Zilucoplan was tested as regimen A of the HEALEY ALS Platform Trial, a phase 2 to 3 multicenter, randomized, double-blind, placebo-controlled perpetual platform clinical trial with sharing of trial infrastructure and placebo data across multiple regimens. Regimen A was conducted from August 17, 2020, to May 4, 2022. A total of 162 participants were randomized to receive zilucoplan (122 [75.3%]) or regimen-specific placebo (40 [24.7%]). An additional 124 concurrently randomized participants were randomized to receive placebo in other regimens. INTERVENTIONS: Eligible participants were randomized in a 3:1 ratio to receive zilucoplan or matching placebo within strata of edaravone and/or riluzole use for a planned duration of 24 weeks. Active drug (zilucoplan, 0.3 mg/kg) and placebo were provided for daily subcutaneous dosing. MAIN OUTCOMES AND MEASURES: The primary end point was change in disease severity from baseline through 24 weeks as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score and survival, analyzed using a bayesian shared-parameter model and reported as disease rate ratio (DRR; \u3c1 indicating treatment benefit). The study included prespecified rules for early stopping for futility. Outcome analyses were performed in the full analysis set comparing the zilucoplan group with the total shared placebo group (n = 164). RESULTS: Among the 162 participants who were randomized (mean [SD] age, 59.6 [11.3]; 99 [61.1%] male), 115 (71.0%) completed the trial. The estimated DRR common to ALSFRS-R and survival was 1.08 (95% credible interval, 0.87-1.31; posterior probability of superiority, 0.24). The trial was stopped early for futility. No unexpected treatment-related risks were identified. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of zilucoplan in ALS, treatment did not alter disease progression. The adaptive platform design of the HEALEY ALS Platform Trial made it possible to test a new investigational product with efficient use of time and resources. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04297683
Serious Neurologic Adverse Events in Tofersen Clinical Trials for Amyotrophic Lateral Sclerosis
No full textINTRODUCTION/AIMS: Tofersen is approved for the treatment of amyotrophic lateral sclerosis (ALS) due to superoxide dismutase 1 mutations (SOD1-ALS). Here we report serious neurologic adverse events (AEs) that occurred in the tofersen clinical trials in people with SOD1-ALS. METHODS: Serious neurologic AEs of myelitis, radiculitis, aseptic meningitis, and papilledema reported in the tofersen clinical trials are described. Serious AEs were defined according to International Conference for Harmonization guidelines, and neurologic AEs in clinical trials were diagnosed by investigators based on symptoms, clinical examination findings, and diagnostic workup. RESULTS: Ten participants (approximately 7% of tofersen 100-mg-treated trial participants) experienced a total of 12 serious neurologic AEs-4 of myelitis, 2 of radiculitis, 2 of aseptic meningitis, and 4 of intracranial hypertension (ICH) and/or papilledema. All events but one resolved either spontaneously, with dosing interruption/modification, or with concomitant therapies. One event was ongoing but improved as of December 2022. While 3 events led to tofersen treatment discontinuation, all other participants were able to remain on treatment. No event was life-threatening or fatal. DISCUSSION: Some antisense oligonucleotides (ASOs) have been described as having pro-inflammatory properties. Aseptic meningitis has been reported with nusinersen; however, myelitis, radiculitis, increased intracranial pressure, and papilledema have not been reported with ASO treatment. These neurologic AEs should be considered when assessing the overall benefit/risk of tofersen treatment for SOD1-ALS. Safety data from the open-label extension and expanded access program will continue to characterize these events and further inform the safety profile of tofersen in SOD1-ALS
Utilizing T1-weighted MRI intensity indices to evaluate in-vivo neurotoxicity in a South African cohort with environmental manganese exposure
No full textBACKGROUND: Excessive exposure to manganese (Mn) causes parkinsonism. Occupational Mn exposure is associated with increased T1-weighted globus pallidus signal on magnetic resonance imaging (MRI) secondary to in-vivo Mn deposition. METHODS: The present study evaluated the T1-weighted pallidal index (PI) as an in-vivo marker of Mn exposure and neurotoxicity in chronic environmental Mn exposure. A total of 53 Black South African participants with a range of residential environmental Mn exposures due to proximity to one of the world\u27s largest smelters underwent T1-weighted MRI. RESULTS: The PI was associated with parkinsonism as measured by the total Unified Parkinson\u27s Disease Rating Scale motor subsection part 3 (UPDRS3) in all participants (β=0.10, confidence interval 0.01, 0.18). Further, the PI was positively associated with total UPDRS3 scores (β=0.14, confidence interval 0.03, 0.25) and the lower limb rigidity subscore (β=0.04, confidence interval 0.005, 0.07) among those who regularly consumed alcohol (\u3e3 drinks/week), but not in those who occasionally consumed alcohol (\u3c3 drinks/week). CONCLUSION: Our findings suggest T1-weighted PI is associated with clinical neurotoxicity in environmental Mn exposure. This association is amplified by regular consumption of alcohol
White matter hyperintensity severity modifies gut metabolite association with cognitive outcomes
No full textBACKGROUND: Gut microbiome-associated metabolites and white matter hyperintensities (WMH) are independently associated with cognitive impairment. However, it is unclear if gut metabolites and WMH interact to influence dementia. OBJECTIVES: To examine the association between gut microbial metabolites and cognitive outcomes and assess whether the severity of baseline WMH would impact associations between gut microbial metabolites and cognitive outcomes. DESIGN: Cross-sectional design. SETTING: Cohort of individuals who are clinically normal, mild cognitive impairment, or Alzheimer\u27s Disease in the Alzheimer\u27s Disease Neuroimaging Initiative (ADNI). PARTICIPANTS: A total of 578 participants with available baseline 3.0T 2D-Fluid Attenuation Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI) scans and baseline gut microbial metabolite measurement were included in the analysis. MEASUREMENTS: Gut metabolite measurements and automated WMH volume estimations were obtained from FLAIR MRI and were used to assess the association and interaction with cognitive impairment. RESULTS: Of 104 metabolites studied, glycodeoxycholic acid (GDCA) surpassed the false discovery rate and was associated the Alzheimer\u27s Disease Assessment Scale-Cognitive Subscale version 13 (ADAS-Cog13) score (β = 0.12, 95 % CI = 0.05-0.20, p = 0.001) and cognitive impairment determined by mini-mental status exam (MMSE) (OR = 2.11, 95 % CI = 1.41-3.15, p \u3c 0.001). GDCA was associated with higher ADAS-Cog13 in participants with low WMH burden (β = 0.21, 95% CI = 0.10-0.32, p \u3c 0.001) but not in participants with high WMH burden (β = 0.04, 95 % CI = -0.07 to 0.14, p = 0.48; interaction p = 0.02). CONCLUSION: An elevated level of GDCA was associated with worse cognition. WMH severity modified the association between GDCA and cognitive outcomes